dbSNP rs41395245: SOCS5:p.Phe19Phe (chr2-46758587-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_144949.3(SOCS5):c.57C>T(p.Phe19Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,611,998 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0021 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0029 ( 16 hom. )

Consequence

SOCS5
NM_144949.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.578

Publications

2 publications found

Variant links:

Genes affected

SOCS5 (HGNC:16852): (suppressor of cytokine signaling 5) The protein encoded by this gene contains a SH2 domain and a SOCS BOX domain. The protein thus belongs to the suppressor of cytokine signaling (SOCS) family, also known as STAT-induced STAT inhibitor (SSI) protein family. SOCS family members are known to be cytokine-inducible negative regulators of cytokine signaling. The specific function of this protein has not yet been determined. Two alternatively spliced transcript variants encoding an identical protein have been reported. [provided by RefSeq, Jul 2008]

SOCS5 links:

LINC01118 (HGNC:49261): (long intergenic non-protein coding RNA 1118)

LINC01118 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 2-46758587-C-T is Benign according to our data. Variant chr2-46758587-C-T is described in ClinVar as Benign. ClinVar VariationId is 720047.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=0.578 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 16 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144949.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SOCS5	NM_144949.3	MANE Select	c.57C>T	p.Phe19Phe	synonymous	Exon 2 of 2	NP_659198.1	O75159
	SOCS5	NM_014011.5		c.57C>T	p.Phe19Phe	synonymous	Exon 2 of 2	NP_054730.1	O75159

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SOCS5	ENST00000394861.3	TSL:1 MANE Select	c.57C>T	p.Phe19Phe	synonymous	Exon 2 of 2	ENSP00000378330.2	O75159
SOCS5	ENST00000306503.5	TSL:1	c.57C>T	p.Phe19Phe	synonymous	Exon 2 of 2	ENSP00000305133.5	O75159
SOCS5	ENST00000861862.1		c.57C>T	p.Phe19Phe	synonymous	Exon 2 of 2	ENSP00000531921.1

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

327

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00308

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00350

Gnomad OTH

AF:

0.00335

GnomAD2 exomes

AF:

0.00201

AC:

500

AN:

249252

AF XY:

0.00206

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00571

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.00281

Gnomad OTH exome

AF:

0.00230

GnomAD4 exome

AF:

0.00290

AC:

4228

AN:

1459738

Hom.:

Cov.:

AF XY:

0.00284

AC XY:

2059

AN XY:

726134

show subpopulations

African (AFR)

AF:

0.000480

AC:

AN:

33356

American (AMR)

AF:

0.00237

AC:

105

AN:

44386

Ashkenazi Jewish (ASJ)

AF:

0.00529

AC:

138

AN:

26068

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000595

AC:

AN:

85720

European-Finnish (FIN)

AF:

0.000187

AC:

AN:

53398

Middle Eastern (MID)

AF:

0.00296

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.00336

AC:

3731

AN:

1111072

Other (OTH)

AF:

0.00265

AC:

160

AN:

60302

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

189

379

568

758

947

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

144

288

432

576

720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00215

AC:

327

AN:

152260

Hom.:

Cov.:

AF XY:

0.00191

AC XY:

142

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.000337

AC:

AN:

41544

American (AMR)

AF:

0.00307

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000622

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000189

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00350

AC:

238

AN:

68012

Other (OTH)

AF:

0.00331

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00320

Hom.:

Bravo

AF:

0.00220

EpiCase

AF:

0.00311

EpiControl

AF:

0.00279

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

0.58

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over